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Combating Disease > The Adaptive Immune System > Flashcards

The Adaptive Immune System Flashcards

1
Q

What are the key characteristics of adaptive immunity ?

A
  • Activated when innate immune defences are overcome
  • Innate immunity is limited by non-specific pattern recognition
  • Adaptive immune system has broad pathogen specific recognition
  • T and B cells (the lymphocytes) use highly specific antigen receptors
    to recognise unique epitopes on antigens (Ags)
  • Unlike innate, adaptive immune cells don’t use pattern recognition. They have specific antigen receptors with a huge diversity of antigen binding specificities (repertoire >109)
  • After first exposure to antigen, clonal selection & expansion of antigen specific B & T cells occurs
  • Long-lived memory T & B cells allow a faster & qualitatively better response on subsequent exposures to same antigen
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2
Q

Where do lymph nodes lie ?

A

At the junctions between lymphatic vessels

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3
Q

How do cells leave the blood?

A

Via small capillaries of & enter lymph tissue

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4
Q

How do cells leave in the absence of pathogens ?

A

It will leave via efferent lymph vessel: Lymphocyte

Recirculation

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5
Q

What happens when a cell encounters an antigen ?

A

It stops recirculating

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6
Q

What do Innate Antigen Presenting Cells (APCs) activate ?

A

Highly specific adaptive immune responses when pathogen overwhelms innate defence

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7
Q

What are dendritic cells ?

A

They are ‘professional’ antigen presenting cells (100x better than macrophage for example)

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8
Q

How do immature dendritic cells mature ?

A

Needs DAMP/PAMP to mature into antigen presenting capacity

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9
Q

What happens when immature skin dendritic cell senses bacterial antigen ?

A

Dendritic cell matures and travels to the draining lymph node

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10
Q

Each lymphocyte has a receptor specific for ?

A

Only one antigen

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11
Q

How do the variable regions of each B & T cell differ ?

A

In amino acid sequence creating a vast variety of binding sites specific for different antigen (& thus different pathogens)

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12
Q

What is surface bound BCR known as ?

A

Immunoglobulin (Ig)

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13
Q

What do B cell receptors bind to ?

A

Epitopes on extracellular antigens on pathogen

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14
Q

Important difference between B cells and T cells ?

A
  • B cells recognise in its native form (can be proteins, carbohydrates or lipids)
  • T cells recognise processed peptides of proteins antigen
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15
Q

Define epitope (antigenic determinant) ?

A

The part of the antigen that binds to the antibody

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16
Q

How can the epitopes be presented on the antigen?

A
  • They can be multivalent (more than one identical epitope per molecule)
  • Or have several different epitopes
17
Q

Epitopes can be ?

A

Linear or discontinuous

18
Q

Structure of immunoglobin (antibody)

A 
- Complementary determining 
region (CDR)
- V regions: Ag binding
- C regions: Interact with effectors
- Heavy Chain 
- Light Chain 
- Fragment antigen binding (Fab)
- Fragment crystalisable, Fc (non-antigen binding)
19
Q

Mewmbrane bound immunoglobulins are

associated with ?

A

Igα & Igβ cytoplasmic tails facilitate intracellular signalling

20
Q

What happens if a lymphocyte comes in contact with its cognate antigen ? and what is this called ?

A
  • It becomes activated & multiplies into a large number of identical cells (clones)
  • This is the Clonal Selection Theory (1960-70’s)
21
Q

What is VDJ recombinant ?

A

Lymphocytes use recombined gene segments to enhanced genetic variability from a limited number of genes

22
Q

What does VDJ stand for ?

A

There are variable (V), diversity (D), joining (J) segments

23
Q

How can B cell diversity be generated ?

A

Before antigen stimulation (Bone Marrow):

  1. Combinatorial diversity: V(D)J somatic gene segment recombination
  2. Junctional diversity: addition/subtraction of nucleotides during recombination process at the joints between the gene segments
  3. Combinatorial diversity of antigen binding site: Many different combinations of Heavy&Light chain V-regions

After antigen stimulation (Lymph nodes):

  1. Somatic hypermutation: Occurs only in B cells that have been activated by antigen
24
Q

Explain V(D)J gene segment somatic recombination ?

A

Heavy chain gene segments:

  • Variable (V)
  • Diversity (D)
  • Joining (J)
  • All anchored by a Constant region (C)

Light chain segments

  • Variable (V)
  • Joining (J)
  • Constant region (C)
  • Two different gene locus encoded on separate chromosomes (22&2)
25
Q

During development of B cells, what happens to C, D and J gene segments ?

A

V, D, J gene segments are

cut & re-spliced by DNA recombination

26
Q

Somatic-V, D, J segments are cut & re-spliced directed by ?

A

Recombination Signal Sequences (RSS) flanking each gene segment

27
Q

What does Recombination Signal Sequences require ?

A
  • Ubiquitous and lymphocyte specific DNA recombination enzymes (V-D-J Recombinase)
  • Recombination activating genes RAG1 & RAG2 are lymphocyte specific components of the V-D-J Recombinase
28
Q

Explain the steps of V(D)J recombination ?

A
  • RAG proteins bind to RSSs & cleave DNA
  • Other proteins process hairpin loops that form after RAG reacts
  • Products include a recombined coding joint & leftover signal joint that is later degraded
29
Q

Why can Junctional diversity be important ?

A

Junctional diversity is an important source of

Ig variability

30
Q

What do RAG complexes introduce ?

A

RAG complex introduces changes in nucleotide

sequence & adds nucleotides (P & N nucleotides) randomly at coding joints

31
Q

What do P & N nucleotides stand for ?

A 
P = Palindromic nucleotides
N = Not encoded in germline by terminal deoxynucleotidyl transferase TdT
32
Q

Define Allelic Exclusion ?

A

Ensures that each B cell synthesises only one heavy.

  • Heavy chains are recombined and expressed first
  • Light-chain recombination then takes place
  • Nonproductive arrangements lead to programmed cell death (apoptosis) during development
33
Q

Structure of TCR compared to BCR ?

A

Very similar however, T cells recognise & bind peptide

antigens derived from pathogen proteins not whole protein, lipid or carbohydrate antigens like B cells

34
Q

What is TCR composed of ?

A

α-chain & β-chain that have germline organisation similar to antibody Heavy & Light chains

35
Q

What is the structure of the TCR ?

A
  • Sequence variation concentrated into 3 CDR
    loops
  • TCR has 1 antigen binding site
  • TCR C region is much simpler (not secreted)
  • α-chain is similar to Ig L-chain with only V & J gene segments
  • β-chain is similar to the Ig H-chain with VDJ gene
    segments
36
Q

What is the difference in terms of Diversity of the TCR?

A

It’s the same

However:

  • Antigen stimulation occurs in the Thymus
  • After antigen stimulation, unlike B cells, T cell diversity doesn’t change
  • TCR are only membrane bound & only recognise antigen.
  • Do not have direct effector functions like secreted antibodies

Combating Disease (11 decks)

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